Controlled environment device

ABSTRACT

The present invention relates to devices and methods for providing controlled environments for surgical procedures, as well as transplantation and wound healing. In particular, one embodiment of the present invention provides devices and methods to provide an anaerobic environment for incision sites. In other embodiments, the present invention provides devices and methods to maintain anaerobic conditions during the collection, transport, and implantation of organs, tissues, cells, and other transplant material. In further embodiments, the present invention provides devices and methods for the production and maintenance of an anaerobic environment surrounding sites of trauma or tissue injury. In particular, the present invention provides devices and methods which allow the operator to strictly control the environment for surgical procedures, transplantation and wound healing, etc. Thus, the present invention also finds use in specialized settings where hyperoxic conditions are desireable.

[0001] This application claims priority benefit to U.S. ProvisionalPatent Application Serial No. 60/241,382, filed Oct. 17, 2000.

FIELD OF THE INVENTION

[0002] The present invention relates to devices and methods forproviding controlled environments for surgical procedures, as well astransplantation and wound healing.

BACKGROUND OF THE INVENTION

[0003] Oxygen, a critical element in many biological systems, wasindependently discovered by Priestly and Sheele in 1774. Shortlythereafter, Lavoisier reported on the poisonous effects of oxygeninhalation and in 1878, Bert documented the poisonous effects of highoxygen tension levels on non-human animals (See, Knight, Ann. Clin. Lab.Sci., 28:331-346 [1998]). Experiments conducted as early as 1899demonstrated that increased oxygen tension results in severe pulmonarycongestion with pneumonia-like changes in mice, rats, and guinea pigs(See, Knight, supra). Indeed, in a 1909 medical text, it is indicatedthat “ . . . there can be little doubt that the administration of oxygenmay not be entirely harmless as stated in previous editions . . . . ”(as quoted by Knight, supra, at page 332). Thus, oxygen toxicity haslong been recognized as a problem in physiological systems. However, theinformation regarding oxygen toxicity remained largely ignored byphysicians for several decades. Significantly, the failure to recognizethe potential toxic effects of increased oxygen tension resulted in anestimated 10,000 cases (worldwide) of blindness in newborns due toretrolental fibroplasia between the 1940s and 1950s (See, Knight,supra).

[0004] Final acceptance of the medical community that increased oxygentension is potentially toxic to humans and other animals did not occuruntil a publication in 1967, which correlated the concentration andduration of inspired oxygen before death with pathologic lung findingsat autopsy. The following year, the formation of pulmonary hyalinemembranes in adults was associated with oxygen toxicity. In 1954, thehypothesis was presented that oxygen poisoning and X-irradiation have acommon basis of action through the formation of oxidizing free radicals(See, Knight, supra). Nonetheless, it was not until the discovery ofsuperoxide dismutase in 1969, that the presence of free radicals inbiological systems was generally considered to be likely.

[0005] Today, the potential for damage caused by oxygen and oxygenradicals is well-recognized. Indeed, oxygen has been referred to as a“double-edged sword,” (See, Knight, supra). Of course, oxygen iscritical for most life forms, including humans. However, in order tobenefit from the advantages provided by aerobic respiration, organismshave developed antioxidant enzymes and other means to detoxify reactionoxygen species and maintain essentially anaerobic conditions throughoutall tissues, organs, and/or the vascular system. Without antioxidantenzymes (e.g., superoxide dismutases such as MnSOD and CuZnSOD), thereis the possibility of damage to many biological molecules (e.g., DNA,RNA, proteins, and lipids). Accumulation of oxidatively damagedmolecules leads to genetic mutations and cellular senescence. Indeed,any factors that compromise the activities of antioxidants may result inthe accumulation of reactive oxygen species and the resultant damagecaused by their action. It has also been suggested that decreasingantioxidant activities is associated with the aging process (See, Tianet al., Free Radical Biol. Med., 24:1477-1484 [1998]).

[0006] Oxygen therapy has been used for decades in various clinicalsettings. However, many essential intracellular reactions involvingoxygen result in the formation of free radicals, and prolonged oxygentherapy is associated with a significant risk of toxicity. For example,exposure to pure oxygen leads to diffuse alveolar damage, with plasmaexudation into the alveolar space. The subsequent death of endothelialand alveolar epithelial cells appear to be essential features ofoxygen-induced alveolar damage, with the damaged cells exhibiting theeffects of apoptosis (condensation and margination of chromatin) andnecrosis (disruption of the plasma membrane) (Barazzone et al., Am. J.Resp. Cell Mol. Biol., 19:573-581 [1998]). Indeed, presentrecommendations indicate that humans should not be exposed to oxygenconcentrations greater than 60% for prolonged time periods (See, Knight,supra).

[0007] In the surgical setting, oxygen toxicity is often observed insituations involving lung injury (e.g., postpneumonectomy pulmonaryoedema [PPO]). PPO may be indistinguishable from severe acuterespiratory distress syndrome (ARDS) or the less serious syndrome, acutelung injury (ALI). PPO is a significant operative concern, with reportsindicating that PPO is a complication in 4-7% of pneumonectomies and 17%of lobectomies, and has an associated mortality rate of 50-100% (See,Williams et al., Eur. Respir. J., 11:1028-1034 [1998]).Ischemia-reperfusion injury has also been considered a contributor toPPO, related to lung damage caused by operative ischemia and injurycaused by formation of reactive oxygen species during reperfusion.Despite improvements in therapies and management, the mortality rate inacute lung injury remains high. While these cases have involved injuriesto lung tissues resulting from exposure to increased oxygen tensions,other organs and tissues have proven to be equally at risk from thistype of exposure. In addition, problems associated with the formation ofadhesions may be related to oxygen exposure of the tissues duringsurgery.

[0008] Oxidative myocardial injury due to oxygen-derived free radicalsand nitric oxide has been shown to occur during hyperoxic (i.e., 300 to400 mm Hg) cardiopulmonary bypass surgery. This has led torecommendations that reduced oxygen tension levels be utilized duringcardiac operations (i.e., “normoxic” levels of about 140 mm Hg) (See,Ihnken et al., J. Thorac. Cardiovasc. Surg., 116:327-334 [1998]). Thishas been shown to be of particular importance in hypoxemic immaturehearts (See, Morita et al., J. Thorac. Cardiovasc. Surg., 110:1235-1244[1995]). Furthermore, reoxygenation of organs such as hearts may alsocause injury (e.g., lipid peroxidation and functional depression) thatmay result in perioperative cardiac dysfunction (Ihnken et al., J.Thorac. Cardiovasc. Surg., 110:1171-1181 [1995]). In addition,cardiopulmonary bypass patients undergoing heart valve replacementsurgery appear to be under oxidative stress, as compared with normalcontrols.

[0009] There are two additional episodes of oxidative stress that occurduring bypass surgery (See, Pepper et al., Free Rad. Res., 21:377-385[1994]). The first is produced when the patient is placed onextracorporeal blood circulation and oxygenation, which results in lipidperoxide and thiobarbituric acid-reactive substance increases. Thesecond episode occurs during reperfusion of the myocardium followingremoval of the aortic cross clamp. This removal ends a period ofischemia and subjects the myocardium to reperfusion or reoxygenationinjury. This injury is amplified by pro-oxidant biochemical changesresulting from extracorporeal oxygenation and blood circulation, as wellas the effects of hemodilution.

[0010] In the central nervous system, oxidative injury can result intremendous damage. For example, oxidative stress has been associatedwith such severe syndromes as Parkinson's disease and Alzheimer'sdisease and familial amyotrophic lateral sclerosis (ALS) (See, Satoh etal., Cell. Mol. Neurobiol., 18:649-666 [1998]).

[0011] The situation is similar in the transplantation setting. Forexample, during long-term in vitro preservation and reperfusion ofhearts for transplantation, irreversible tissue damage occurs due toreactive oxygen species. Thus, efforts have been made to inhibit thegeneration of oxygen-derived free radicals and the associated oxidativedamage of ischemic tissue through the use of cold conditions andspecially formulated buffer solutions (See, Sellke et al., J. Surg.Res., 80:171-176 [1998]; Cargnoni et al., J. Heart Lung Transplant.,18:478-487 [1999]). Nonetheless, the time limits for donor organtransport remain limited to several hours.

[0012] Thus, it is clear that what is needed are improved methods anddevices that reduce the potential for oxidative injury during surgicalprocedures, as well in the transport of samples, organs/tissues, etc. Itis also clear that improved methods are needed which allow the operator(i.e., surgeon) to carefully control and monitor the gases in thetheater surrounding a surgical field as appropriate for the surgicalprocedure.

SUMMARY OF THE INVENTION

[0013] The present invention relates to devices and methods forproviding controlled environments for surgical procedures, as well astransplantation and wound healing. In particular, one embodiment of thepresent invention provides devices and methods to provide an anaerobicenvironment for incision sites. In other embodiments, the presentinvention provides devices and methods to maintain anaerobic conditionsduring the collection, transport, and implantation of organs, tissues,cells, and other transplant material. In further embodiments, thepresent invention provides devices and methods for the production andmaintenance of an anaerobic environment surrounding sites of trauma ortissue injury. In particular, the present invention provides devices andmethods which allow the operator to strictly control the environment forsurgical procedures, transplantation and wound healing, etc. Thus, thepresent invention also finds use in specialized settings where hyperoxicconditions are desirable.

[0014] The present invention provides devices for maintaining a surgicalfield in an isolated environment comprising an enclosure for separatinga surgical field from an atmosphere ambient to the device, and at leastone access port, wherein the access port enables admission into theenclosure. In one embodiment, the at least one access port enablesadmission of at least one surgical means into the enclosure. In anotherembodiment, the surgical means is selected from the group consisting ofsurgical instruments, robotics, sensors, and human hands. In anotherembodiment, the devices of the present invention comprise means forevacuating the isolated environment. In one particularly preferredembodiment, the evacuating produces an environment with reduced oxygentension. In an alterative preferred embodiment, the reduced oxygentension within the device is essentially oxygen-free. In yet anotherembodiment, the devices of the present invention further comprise meansfor refilling the isolated environment. In one preferred embodiment, therefilling produces an environment with reduced oxygen tension, while inanother preferred embodiment, the reduced oxygen tension is essentiallyoxygen-free. In an alternative embodiment, the refilling produces anenvironment with an increased oxygen tension. In yet an additionalembodiment, the devices of the present invention further comprise meansfor filling the isolated environment, while in alternative embodiments,the filling produces an environment with reduced oxygen tension. In somepreferred embodiments, the filling produces an environment with anincreased oxygen tension. In other particularly preferred embodiments,the isolated environment is essentially pathogen-free. In still otherpreferred embodiments, the devices of the present invention furthercomprise a transport attachment. In some particularly preferredembodiments, the transport attachment is lockingly engaged to thedevice, while in other particularly preferred embodiments, the transportattachment is detachably engaged to the device. In still furtherparticularly preferred embodiments, the transport attachment has areduced oxygen tension.

[0015] The present invention also provides devices for maintaining aninjured area in an isolated environment comprising an enclosure forseparating an injured area from the atmosphere ambient to the device,wherein the oxygen tension of the isolated environment is controllable.In some embodiments, the devices comprise at least one access port. Inalternative embodiments, the devices further comprise means forevacuating the isolated environment. In still other embodiments, theevacuating comprises means for oxygen release and retention of a heavygas within the isolated environment. In some particularly preferredembodiments, the evacuating produces an environment with reduced oxygentension, while in other particularly preferred embodiments, the reducedoxygen tension is essentially oxygen-free. In additional embodiments,the devices further comprise means for refilling the isolatedenvironment. In one preferred embodiment, the refilling produces anenvironment with reduced oxygen tension, while in another preferredembodiment, the reduced oxygen tension is essentially oxygen-free. In analternative embodiment, the refilling produces an environment with anincreased oxygen tension. In yet an additional embodiment, the devicesof the present invention further comprise means for filling the isolatedenvironment, while in alternative embodiments, the filling produces anenvironment with reduced oxygen tension. In some preferred embodiments,the filling produces an environment with an increased oxygen tension. Inother particularly preferred embodiments, the isolated environment isessentially pathogen-free. In still other preferred embodiments, thedevices of the present invention further comprise a transportattachment. In some particularly preferred embodiments, the transportattachment is lockingly engaged to the device, while in otherparticularly preferred embodiments, the transport attachment isdetachably engaged to the device. In still further particularlypreferred embodiments, the transport attachment has a reduced oxygentension. In other particularly preferred embodiments, the injured areais selected from the group consisting of surgical incisions, burns,lesions, and broken bones.

[0016] The present invention also provides means for maintainingmaterial (i.e., material of interest) in an isolated environmentcomprising an enclosure for separating the material from an atmosphereambient to the device, wherein the oxygen tension of the isolatedenvironment is controllable. In one preferred embodiment, the devicescomprise at least one access port. In another preferred embodiment, thedevices further comprise means for evacuating the isolated environment.In still other embodiments, the evacuating comprises means for oxygenrelease and retention of a heavy gas within the isolated environment. Insome particularly preferred embodiments, the evacuating produces anenvironment with reduced oxygen tension, while in other particularlypreferred embodiments, the reduced oxygen tension is essentiallyoxygen-free. In additional embodiments, the devices further comprisemeans for refilling the isolated environment. In one preferredembodiment, the refilling produces an environment with reduced oxygentension, while in another preferred embodiment, the reduced oxygentension is essentially oxygen-free. In an alternative embodiment, therefilling produces an environment with an increased oxygen tension. Inyet an additional embodiment, the devices of the present inventionfurther comprise means for filling the isolated environment, while inalternative embodiments, the filling produces an environment withreduced oxygen tension. In some preferred embodiments, the fillingproduces an environment with an increased oxygen tension. In otherparticularly preferred embodiments, the isolated environment isessentially pathogen-free. In still other preferred embodiments, thedevices of the present invention further comprise a transportattachment. In some particularly preferred embodiments, the transportattachment is lockingly engaged to the device, while in otherparticularly preferred embodiments, the transport attachment isdetachably engaged to the device. In still further particularlypreferred embodiments, the transport attachment has a reduced oxygentension. In yet other particularly preferred embodiments, the materialis transplant material. In still other particularly preferredembodiments, the transplant material is selected from the groupconsisting of organs, tissues, cells, and artificial materials. In anadditional embodiment, the maintaining comprises transporting thematerial.

DESCRIPTION OF THE FIGURES

[0017]FIG. 1 is an overall perspective view of one embodiment of thecontrolled environment device of the present invention. In particular,this Figure provides an overall perspective view of one embodiment of acontrolled surgical environment of the present invention,

[0018]FIG. 1A provides an enlarged cross-sectional view of the base padportion of the controlled environment device shown in FIG. 1.

[0019]FIG. 2 is an enlarged perspective view of the airlock of oneembodiment of the controlled environment device of the presentinvention.

[0020]FIG. 3 is an overall perspective view of one embodiment of thecontrolled environment transport device of the present invention. Inparticular, this Figure provides an overall perspective view of onecontrolled environment transport device of the present invention.

[0021]FIG. 4 is an overall perspective view of one embodiment of thecontrolled environment device of the present invention. In particular,this Figure provides an overall perspective view of one controlledenvironment trauma bandage embodiment of the present invention.

[0022]FIG. 4A provides an enlarged cross-sectional view of the base padof the controlled environment device shown in FIG. 4.

DESCRIPTION OF THE INVENTION

[0023] The present invention relates to devices and methods forproviding controlled environments for surgical procedures, as well astransplantation and wound healing. In particular, one embodiment of thepresent invention provides devices and methods to provide an anaerobicenvironment for incision sites. In other embodiments, the presentinvention provides devices and methods to maintain anaerobic conditionsduring the collection, transport, and implantation of organs, tissues,cells, and other transplant material. In further embodiments, thepresent invention provides devices and methods for the production andmaintenance of an anaerobic environment surrounding sites of trauma ortissue injury. In particular, the present invention provides devices andmethods which allow the operator to strictly control the environment forsurgical procedures, transplantation and wound healing, etc. Thus, thepresent invention also finds use in specialized settings where hyperoxicconditions are desirable.

[0024] In particularly preferred embodiments, the present inventionprovides methods and devices to protect the interior of the body fromdiatomic oxygen (i.e., O₂) or superoxygen radicals (e.g. superoxide O₂⁻) during surgery, as well as during harvesting and/or implantation oforgans or cells. Thus, the present invention helps prevent the injuryassociated with oxygen toxicity to vital organs (e.g., heart, lungs, andcentral nervous system).

[0025] In one embodiment, the devices of the present invention provide acontrolled surgery environment that surrounds the surgical field fromthe time prior to the actual surgery to after the conclusion of surgery.Importantly, the present invention allows ready access to the surgicalfield by the surgeon, nurses, and others involved in the procedure, aswell as allowing insertion of instruments, monitoring instruments,devices, sampling materials (e.g., for microbiological cultures,biopsies, etc.), implantable devices (e.g., pacemakers, bone pins,hearing devices, etc.), and donor tissues/organs without compromisingthe integrity of the surgical field. In some embodiments, the presentinvention provides a controlled environment for surgical procedures suchas Caesarian sections. In these embodiments, the device used is largerthan many other embodiments in order to accomodate the size of themother's abdomen and allow sufficient room for the surgical team towork. In addition, in some cases, the incision area will be quite large.Thus, the actual surface of the adhesive in contact with the mother'sskin may be relatively small. In preferred embodiments, there is anairlock and/or transport device docked with the controlled surgicalenvironment. The airlock and/or transport device are used to remove thebaby from the controlled surgical environment. When the transport deviceis used, it can be charged with a gas mixture that is appropriate forthe baby.

[0026] In certain preferred embodiments, the maintenance of an anaerobicenvironment around the surgical incision or trauma site prevents theintroduction or exposure of oxygen into the tissues or organs, as wellas preventing microbial contamination of the site. Indeed, the presentinvention provides an aseptic, oxygen-controlled surgical “theater” forthe performance of surgeries.

[0027] It is not intended that the present invention be limited tosituations in which a reduced oxygen tension or essentially anaerobicenvironment is desireable. Indeed, it the present invention providesadvantages in cases where it is necessary or desireable for theenvironment surrounding a surgical field be strictly controlled. Forexample, it is contemplated that the present invention will find use incases (e.g., certain surgeries) where hyperoxic conditions aredesireable. In addition, it is contemplated that the present inventionwill find use in cases where modified concentrations of other gases aredesireable. For example, it is contemplated that the present inventionwill be used in cases where increased or decreased nitrogenconcentrations are favored. In sum, the present invention provides themeans to control the environment surrounding a surgical area (i.e., the“surgical theater”).

[0028] It is not intended that the present invention be limited to anyparticular size or configuration. Indeed, the shape and size of thedevice is largely dependent upon the particular procedure to beperformed using the device or the particular reason for using thedevice. For example, in some cases, a larger dome is needed, while inothers a smaller dome is preferred. In addition to the dome size, otherdesign considerations are contemplated. Thus, any shape, size, orconfiguration of the present invention is contemplated, so long as theenvironment within the device is controllable and/or optimal for theprocedure being conducted or the particular reason for using the device.

[0029] Furthermore, although preferred embodiments of the presentinvention involve human patients, it is not intended that the presentinvention be limited to use with humans. Indeed, it is contemplated thatthe present invention will find use in the veterinary setting as well asthe clinical setting. In addition, it is contemplated that the presentinvention will find use both in established surgical centers as well asin the field.

Controlled Surgery Environment (CSE)

[0030] In one preferred embodiment of the invention, as illustrated inFIG. 1, the controlled surgery environment (CSE) (100) comprises aninflatable, flexible transparent plastic dome (101). This surgery domecan be easily collapsed into a flat package for storage prior to use andfor disposal. Indeed, it is contemplated that the devices of the presentinvention will find use as disposable (i.e., one use) CSEs. However, itis contemplated that the devices will be decontaminated following useand reused as needed or desired. In addition, it is not intended thatthe present invention be limited to an embodiment in which the CSE iscollapsed (i.e., evacuated) prior to its use. Thus, in some embodiments,the CSE is evacuated of any gas within the dome and then filled with thedesired gas prior to the beginning of surgery.

[0031] A pad (102) on the package has a sterile adhesive (103) with abacking (104) that can be removed to expose the sterile adhesive (103).In preferred embodiments, the collapsed (i.e., evacuated) pad ispositioned over the surgical field such that the surgery grooves (105)are in alignment with marks drawn on the patient's skin during surgicalpreparation to delineate the surgical field. Prior to beginning thesurgical procedure itself, the backing (104) is removed and the pad(102) is pressed on to the patient such that the adhesive (103) securelybinds to the patient's skin in the proper orientation.

[0032] Sterile, gas (e.g., nitrogen, argon, or other suitable gases)supplied by an attached compressed gas cylinder (106) or via an inletfor another source (108), is introduced into the CSE by means of a gassupply inlet (107) to inflate the surgery dome (101). A gas pressurevalve and regulator (109) mounted on the CSE is used to control theamount of gas introduced into the CSE and to maintain a positivepressure on the dome, thereby preventing unwanted gas (e.g., oxygen) andmicroorganisms from entering into the surgical theater. By placing theCSE over the surgical field and filling it with nitrogen (or anothersuitable gas or combination of gases) prior to exposing the internalorgans to the environment, the risk of oxygen toxicity and microbialcontamination are greatly reduced. Thus, in some particularly preferredembodiments, the present invention prevents the contamination of thesurgical field by oxygen and microorganisms from the time that thebody's internal organs are exposed until after the incision is closed.

[0033] Surgical personnel insert their hands into the CSE by eitherinserting their pre-gloved hands through an elastic iris membrane (110)in the appropriate access ports (111), or into gloves (112) that are anintegral part of the dome (101). In addition to the surgeon's accessports, in preferred embodiments, there are ports (113) available forsurgical assistants (e.g., nurses, additional surgeons, assistants,etc.). As with the surgeon's access ports, these ports may also befitted with gloves (not shown). In particularly preferred embodiments,the iris membranes collapse to seal off the dome when it is not in useand compress tightly around a gloved arm placed inside the CSE. However,it is not intended that the present invention be limited to access byhuman hands. For example, it is contemplated that mechanical devices,including but not limited to robots, fiber optics, and lasers will beused in conjunction with the present invention. In some embodiments,entry of these mechanical devices into the interior of the CSE isachieved through any of the access ports present in the invention. Inother embodiments, access is achieved through ports that are speciallytailored to the device.

[0034] In some embodiments, once the personnel's hands are inside thedome (101), the appropriate surgical instrument(s) (114) may be selectedfrom an integral instrument storage area (115) inside the dome. Inalternative embodiments, the instruments are received through an airlock(116) positioned on the side of the dome. In some embodiments, theairlock is an iris self-sealing membrane that conforms to theinstruments as they are passed into the dome. In other embodiments, theairlock mechanically attaches to an external controlled transportenvironment (CTE).

[0035] A preferred embodiment of an airlock of the present invention isprovided in FIG. 2. In this Figure, the wall of the CSE (201) whichleads into the interior (202) of the CSE is shown. The airlock matingbaffle (203) is indicated, as is the airlock mating zipper (204),airlock evacuation nozzle and cut-off valve (205), CSE access zipper(206), and CSE access port (207).

[0036] Surgical instruments, tissues, organs, and/or other neededsupplies or equipment are placed inside the CTE prior to the beginningof surgery. In some preferred embodiments, the CTE is attached to theCSE prior to the expulsion of air and the introduction of inert sterilegas. Thus, in these embodiments, the CTE is also evacuated at the sametime as the CSE. As with instruments, tissues for grafting and organsfor transplantation may also be passed through the airlock (116; asshown in FIG. 1) or placed within a storage area (not shown) within thedome prior to the beginning of the surgical procedure.

[0037] In some embodiments, once ready to begin the actual operation,the surgeon or other personnel pulls the surgical area pull tab in thebase pad (117) to draw the surgical area pull wire (118) into apre-defined pattern, thereby exposing the surgical field on thepatient's body to the controlled surgery environment and provide thesurgeon access to the incision site.

[0038] During the operation, blood and other liquids are removed fromthe surgical field by a suction hose (119) connected to an externalsuction pump. Clamps and other surgery fixtures may be attached asneeded, to the base pad by means of retractor anchors (120). Thesefixtures are connected to the dome in a manner such that the integrityof the controlled environment is not compromised.

[0039] In another embodiment, the surgeon (or another member of thesurgery team) makes at least one incision directly through the base pad.In this embodiment, only the interior of the body is exposed to theatmosphere of the CSE. No exterior portions of the body (e.g., the skin)are exposed to the interior of the CSE, thereby further reducing thepotential for contamination of the incision(s) or internal organs by thepatient's skin flora.

[0040] In cases of unexpected complications during the surgicalprocedure, the present invention is designed so that the surgeon orother personnel can quickly remove the dome from the patient. Thisallows the access of additional personnel to the surgical field, as wellas the use of equipment that does not fit within the confines of thedome. In such cases, the surgeon or other personnel pulls the emergencyaccess zipper tab (121) along the emergency access pull zipper seam(122), which separates the dome from its base. Although this destroysthe integrity of the surgical field as the internal organs are exposedto ambient air, this may be required in some cases.

[0041] The present invention is not limited to any particular materialor embodiment. Indeed, the CSE and CTE can be made out of any suitablematerial. For example, although plastics are lighter and perhaps easierto work with, it is intended that materials such as plexiglass and othermaterials will be useful in the present invention. Indeed, it isintended that flexible materials as well as rigid materials will finduse in the present invention. Also, in other embodiments, the surgeon,other personnel, and/or mechanical devices are provided access to thesurgical field by means of ports positioned on the top of the CSE. Insuch embodiments, a controlled environment can be created by providing ahigh flow of sterile nitrogen (or other appropriate gas) inside thewalls of the CSE, thereby preventing unwanted gas (e.g., oxygen) fromcoming into contact with the patient's internal organs or the surgicalfield.

[0042] In alternative embodiments, the gas utilized in conjunction withthe present invention provides an increased oxygen concentration, ascompared to the ambient environment. Although it is recognized thatanaerobic conditions are typically preferred for surgical methods inwhich internal organs are exposed to the ambient environment, it iscontemplated that in certain settings involving skin and otherexternally located organs, hyperoxic conditions are preferred. Thus, thepresent invention provides the means to produce such conditions in ahighly controllable manner. In addition, the conditions can be adjustedas the device is being used, thereby optimizing the gas concentrationand composition for each stage of a surgical procedure. Thus, thepatient receives the most appropriate gas concentration and compositionfor the particular surgery and patient involved.

[0043] In addition, it is contemplated that the CSE integrity may bemaintained after completion of surgery. For example, in some embodimentsthe CSE is maintained through the post-operative period and/or throughsome or all of the recovery period. Thus, it is possible to maintain thecontrolled environment surrounding a surgical incision for the optimumamount of time to speed proper healing.

Controlled Transport Environment (CTE)

[0044] The present invention also provides a controlled transportenvironment (CTE) suitable for the storage and transport of organs,tissues and cells. In particular, this embodiment is suited for use withorgans and tissues for transplantation. For example, organs harvestedfrom a donor and placed within an CTE are maintained in the CTE untiltransplanted in a recipient. In particularly preferred embodiments, theorgans are harvested and transplanted using the CSE of the presentinvention under anaerobic conditions, with the CTE docked to the CSE(i.e., via the airlock, for example, as shown in FIG. 2). In thismanner, the organs are never exposed to atmospheric oxygen and thechances for oxidative injury are greatly reduced. In addition, thechances of microbial contamination of the organs and transplant site areminimized.

[0045] The removal, preparation and transport of organs and tissuesremains an extremely problematic aspect of transplant surgery,particularly for organs such lungs, livers, and hearts. As brieflydiscussed above, the removal of organs from their normal, anaerobicenvironment within the body and exposure to oxygen results in oxidativedamage to these organs. Indeed, the damage can be sufficient to renderthe organs unusable for transplantation purposes. The sameconsiderations are involved in the harvesting, transportation andimplantation of graft tissues and cells.

[0046] The CTE of the present invention provides a complete,self-contained controlled environment for the transport of tissues andorgans between a donor and recipient. In particularly preferredembodiments, the CTE is docked via the airlock to the CSE in which thedonor organs/tissues are removed, and the organs/tissues placed withinthe CTE under anaerobic conditions. The CTE is then sealed andtransported to the site of the transplantation to the recipient. The CTEcontaining the organs/tissues is then docked to the CSE in which therecipient is to undergo surgery under anaerobic conditions. Theorgans/tissue are then removed from the CTE and implanted into therecipient. In this manner, the use of the CSEs and CTE maintains theorgans/tissues in a sterile anaerobic environment. In addition, the useof the CTE allows the organs/tissues to enter the CSE while maintainingthe integrity of the CSE.

[0047]FIG. 3 provides a schematic of a preferred embodiment of the CTEof the present invention. The CTE (300) has an inflatable, flexibleplastic dome (301) attached to a semi-rigid base pad (302). In somepreferred embodiments, the plastic of the dome (301) is transparent,although in alternative embodiments, the plastic is translucent oropaque. The CTE is initially collapsed (i.e., with no air present in itsinterior) prior to use. Sterile, gas (e.g., nitrogen, argon, othersuitable gas, and/or mixture of gases) supplied by an attachedcompressed gas cylinder (303) or via an inlet for another source (305),is introduced into the CSE by means of a gas supply inlet (304) toinflate the surgery dome (301). A gas pressure valve and regulator (306)mounted on the CSE is used to moderate the amount of gas introduced intothe CSE. The valve and regulator (306) serve to maintain a positivepressure on the dome, thereby preventing unwanted gas (e.g., oxygen) andmicroorganisms from entering into the surgical theater. In oneembodiment, the valve and regulator functions to cut off the gas supplyafter inflation, sealing the gas inside the CTE. This allows thetransport of the CTE without an attached gas cylinder or external gassupply.

[0048] At an appropriate time during surgery to remove a donor organ ortissue, the CTE is attached to an CSE by aligning its airlock matingbaffle (307) with the CSE's airlock mating baffle (shown as (203) inFIG. 2), and engaging the CTE's airlock mating zipper (308) to seal thebaffles together. This creates an airtight airlock between the CSE andCTE. A vacuum hose is then attached to the airlock evacuation nozzle andvalve (309) and the air within the airlock is removed, therebycollapsing it. Then, a gas supply hose is attached to the airlockevacuation nozzle and valve and the airlock is inflated with sterile gas(e.g., anaerobic gas).

[0049] At this point, the access port on the CSE side of the airlock(shown as (207) in FIG. 2) is opened and the surgeon or assistantreaches into the airlock to the CTE access port zipper (310). Operatingthe zipper (310) opens the CTE access port (311) to fully connect theCTE and CSE. The organ(s) and/or tissue(s) are transferred from thedonor into the appropriate cavities formed by the organ/tissuecontainment baffles (312) of the CTE. The blood/blood substitutedelivery hose (313) and blood/blood substitute removal hose (314) maythen be attached to appropriate arteries and/or veins in the harvestedorgans, if desired that the organ be supplied with cooled fluid duringtransport. In some embodiments, the fluid is oxygenated blood (e.g.,normoxic blood), while in other embodiments, a blood substitute is used.Finally, the airlock unsealing process is reversed, first to seal theCTE and then to seal the CSE, and finally to detach the CTE from theCSE. The CTE is then transported to the site of the transplantoperation, where it is docked to the CSE used in the transplantoperation. Docking is accomplished using the same procedures asdescribed for harvesting the organ(s)/tissue(s). The organ(s)/tissue(s)are removed from the CTE and the transplant operation is completed.During all phases of this process, the oxygen trap/exhaust (315) is usedto either trap and hold or exhaust any trace oxygen that has remained inthe CTE or its airlock from the initial filling and airlock mating, orthat has outgassed from the inside surface of the CTE.

[0050] The CTE is also suited for use as a container to anaerobicallycondition and then transport surgical instruments, fixtures, devices,sensors, pacemakers, other implantable devices, etc., into an CSE viathe airlock. In addition, it is contemplated that the CTE of the presentinvention will find use alone as a device to transport organs, tissuesand cells, without the use of the CSE. In these cases, the instruments,devices, organs, tissues, cells, etc., are placed in the CTE under usualaerobic conditions and the CTE is evacuated via its gas supply inlet(304) and valve (306), and then filled with sterile gas (e.g., anaerobicgas). Pre-packaged surgery instruments may also be stored in anevacuated condition (e.g., anaerobically) in CTEs and the CTEs inflatedas needed.

Controlled Environment Trauma Bandage (CETB)

[0051] The present invention also provides a controlled environmenttrauma bandage (CETB) suitable to produce and maintain a controlledenvironment over a trauma site. As shown in the preferred embodimentillustrated in FIG. 4, this embodiment is similar to the CSE in that thebandage provides a controlled environment that can be positioned overthe site of an injury or incision. The CETB (400) comprises aninflatable, flexible transparent plastic dome (401). This dome can beeasily collapsed into a flat package for storage prior to use and fordisposal. Indeed, it is contemplated that the devices of the presentinvention will find use as disposable (i.e., one use) CETBs. However, itis contemplated that the devices will be decontaminated following useand reused as needed or desired. A pad (402) on the package has asterile adhesive (403) with a removable backing (404) that can beremoved to expose the sterile adhesive (403). The pad is positioned overthe trauma site, such that the site is covered by the dome of the CETB,and the pad (402) is pressed on to the patient such that the adhesivebacking (403) securely binds to the patient's skin in the properorientation.

[0052] Sterile, anaerobic gas (e.g., nitrogen, argon, or another desiredgas) supplied by an attached compressed gas cylinder (405) or via aninlet for another external source (not shown), is introduced into theCETB by means of a gas supply inlet (406) to inflate the CETB dome(401). A gas pressure valve and regulator (407) mounted on the CSE areused to moderate the amount of gas introduced into the CETB. The valveand regulator (407) serve to maintain a positive pressure on the dome,thereby preventing unwanted gas (e.g., oxygen) and microorganisms fromentering into CETB. In some embodiments, the collector (408) trapsoxygen, while in other embodiments the collector (408) preferentiallyallows the escape of oxygen out of the dome, while restricting orpreventing the escape of a heavy gas (e.g., nitrogen). Thus, the presentinvention prevents the contamination of the trauma site. As with theCSE, the CETB is not limited to any particular material or embodiment.Indeed, the CETB can be made out of any suitable material.

Definitions

[0053] As used herein, the term “anaerobic” refers the absence ofoxygen, while the term “aerobic” refers to the presence of oxygen. Asused herein, the term “essentially anaerobic” refers to environments inwhich there is minimally detectable oxygen.

[0054] As used herein, the term “altered oxygen tension” refers to anenvironment in which the oxygen tension is different from that of theambient atmosphere. In particularly preferred embodiments, the oxygentension is less than that of the ambient atmosphere.

[0055] As used herein, the term “reduced oxygen tension” refers to anenvironment in which the oxygen tension is less than that of the ambientatmosphere. In some embodiments, the term refers to E_(h) (i.e.,oxidation-reduction potential) values less than 125 mv, while in otherembodiments, the term refers to E_(h) values of −150 to −250 mv, whilein other embodiments, the term refers to E_(h) values of less than −250mv. In other embodiments, the term refers to reduced oxygenconcentrations. For example, in preferred embodiments, the oxygenconcentration of the isolated environment is less than 20 parts permillion of dissolved oxygen. However, it is not intended that thepresent invention be limited to any particular oxygen concentration.

[0056] As used herein, the term “increased oxygen tension” refers to anenvironment in which the oxygen tension is greater than that of theambient atmosphere. In some embodiments, the term refers to E_(h) valuesgreater than 250 mv.

[0057] As used herein, the term “oxygen-free” refers to the absence ofdetectable oxygen.

[0058] As used herein, the term “hyperoxia” refers to an excess ofoxygen in the system of interest (e.g., tissue, an organ or body), whilethe term “hypoxia” refers to a decreased concentration of oxygen in thesystem of interest. While used to describe an isolated environment, theterm hyperoxia refers to an oxygen concentration that is greater thanthat of the ambient atmosphere (i.e., outside of the isolatedenvironment), wihle hypoxia refers to an oxygen concentration that isless than that of the ambient atmosphere (i.e., outside of the isolatedenvironment).

[0059] As used herein, the term “normoxic” refers to an oxygenconcentration that is normal for the tissue and/or organ of interest. Insome cases, normoxic conditions are those in which no oxygen is present(e.g., deep internal organs), while in other situations, the termencompasses relatively high oxygen concentrations (e.g., the skin or eyesurfaces). Thus, it is intended that the term encompass the normaloxygen concentration for the location or site of interest. When used todescribe an isolated environment, the term refers to an oxygenconcentration that is the same as that of the ambient atmosphere (i.e.,outside of the isolated environment), such as the oxygen concentrationunder standard conditions.

[0060] As used herein, the term “hypernitric” refers to a nitrogenconcentration that is greater than of the ambient atmosphere, while theterm “hyponitric” refers to a nitrogen concentration that is less thanthat of the ambient atmosphere. In preferred hyponitric environments,nitrogen is minimally detectable. As with oxygen, the terms may also beused in reference to the amount of nitrogen present in an in vivo systemor in a cell, organ, tissue, etc.

[0061] As used herein, the term “controlled environment” refers to anenvironment that is regulated by an operator, so as to provide thedesired environmental conditions within a controlled environment device.Thus, it is intended that the term encompass environments withincontrolled environment devices that are optimum for surgical procedures(e.g., CSEs), transport of specimens, transplant materials, etc. (e.g.,CTEs), and healing (e.g., CETBs).

[0062] As used herein, the terms “radical” and “free radical” refer toatoms, molecules, or compounds that contain an unpaired electron. Theterms encompass, but are not limited to oxygen radicals (e.g.,oxyradicals).

[0063] As used herein, the term “oxidative stress” refers to conditionsin which oxidation presents a threat to biological or other systems,including but not limited to cells, tissues, organs, etc. For example,under such conditions, the presence of oxygen has detrimental effects onthe structure, function, and/or physiology of the biological systeminvolved. In addition, the term encompasses the detrimental effects ofoxygen on inanimate objects.

[0064] As used herein, the term “surgical theater” refers to the spacedirectly surrounding and in close proximity to the surgical field. Thus,surgical personnel operate within the surgical theater. In preferredembodiments, the term encompasses the surgical field and surroundingspace. In particularly preferred embodiments, the surrounding spaceencompasses the interior of a CSE, CTE or CTEB.

[0065] As used herein, the term “surgical field” refers to the area inwhich surgical personnel are conducting a surgical procedure. It isintended that the term encompass the incision site as well as anyinternal areas within the surgical patient that are exposed to theoutside environment due to the incision.

[0066] As used herein, the term “surgery” refers to any medicalintervention that involves cutting or tearing the skin or other organs.In many cases, the cutting or tearing results in the exposure ofinternal organs and/or tissues to the environment. It is not intendedthat the term be limited to any particular type of surgical procedure.Indeed, it is intended that the term encompass microscopically-aidedsurgery (e.g., arthroscopic surgery), as well as stereotactic and othersurgical methods.

[0067] As used herein, the term “surgical means” refers to any item thatcan be used to perform or assist with surgery. It is intended that theterm encompass human hands, as well as surgical instruments, lasers,robotics, remote-controlled surgical instruments,microprocessor-controlled instruments, sensors (e.g., electronic andother equipment used to assist the surgical team in assessing the statusof the patient), monitors (e.g., monitors for vital functionmeasurements, etc.), etc. Thus, it is not intended that the presentinvention be limited to any particular means for performing or assistingsurgery.

[0068] As used herein, the term “transplantation” refers the transfer ofan organ and/or tissue from one human or non-human animal (i.e., a“donor”) to another human or non-human animal (i.e., a recipient). It isnot intended that the donor and/or recipient be limited to humans.Indeed, it is intended that the donor and/or recipient be of anyspecies. In addition, the term encompasses the introduction of syntheticor materials prepared in vitro, for use in transplantation. For example,the term encompasses the use of synthetic or artificial substances(e.g., bone and skin). In addition, the term encompasses theintroduction of artificial devices or prosthetics (e.g., heart valves,stents, joints, monitors, pacemakers, etc.). The term “transplant”refers to the material (organ, tissue, cells, artificial substances,devices, etc.) to be transplanted.

[0069] As used herein, the term “graft” refers to a portion of tissue ora collection of cells that is suitable for implantation ortransplantation. It is intended that the term encompass any graftmaterial and types, including but not limited to autologous, avascular,accordion, autodermic, autoepidermic, bone, fascicular, full-thickness,heterologous, heteroplastic, xenografts, nerve, muscle, tendon,ligament, synthetic, and other suitable grafts, including graftsobtained from biological material grown in vitro. The term “grafting”refers to the process of implanting or transplanting a graft.

[0070] As used herein, the term “ischemia” refers to a deficiency ofblood in a part, often due to functional or actual constriction orobstruction of a blood vessel.

[0071] As used herein, the term “perfusion” refers to the passage ofliquid over and/or through an organ, while the term “reperfusion” refersto the passage of liquid over an/or through an organ which waspreviously unperfused (e.g., an artery clamped during surgery to preventpassage of blood).

[0072] As used herein, the term “isolated environment” refers to anenvironment that is separated from the ambient atmosphere by means of anenclosure. In particularly preferred embodiments, the isolatedenvironment of the present invention has a reduced oxygen tension and isessentially pathogen-free.

[0073] As used herein, the term “pathogen-free” refers to the absence ofpathogenic organisms, including, but not limited to bacteria, viruses,prions, fungi, and parasites.

[0074] As used herein, the term “flexible” refers to an item that ispliable and movable. In preferred embodiments of the present invention,the term refers to devices with plastic or vinyl enclosures.

[0075] As used herein, the term “rigid” refers to an item that is stiff(i.e., hard) and not pliable. In some embodiments of the presentinvention, the devices are composed of hard, non-pliable materials(e.g., some plastics).

[0076] As used herein, the term “iris membrane” refers to an irisdiaphragm configuration. In preferred embodiments, the iris membranefunctions to expand only to the desired size to allow the passage of asurgical means, etc. into or out of the controlled environment of thepresent invention. In some embodiments, the iris is composed of multipleoverlapping flaps of material. However, in preferred embodiments, theiris membrane is composed of one piece of flexible material. The irismembrane of the present invention is flexible enough to allow thepassage of a surgical means, but when coupled with the positive internalpressure of the CSE, prevents the leakage of air into the interior ofthe controlled environment of the present invention.

[0077] As used herein, the term “transport attachment” refers to eitheran integral portion of a CSE or CTE. In preferred embodiments, the CTEis attached to a CSE by means of a locking port, which prevents theintroduction of air into either the CSE or the CTE. In embodiments inwhich the CTE is provided as an integral portion of a CSE, the CTE isdetachably engaged to the CSE, such that it may be removed from the CSEas needed. or desired. In particularly preferred embodiments, thetransport attachment is useful for providing sterile, anaerobicallyprepared surgical instruments and transplant materials.

[0078] In summary, the present invention provides numerous advances andadvantages over the prior art, including improved methods and devicesfor surgery performed under conditions to minimize oxidative damage toexposed tissues. All of these advantages enhance the surgical outcomewhen the device and methods of the present invention are used.

[0079] All publications and patents mentioned in the above specificationare herein incorporated by reference. Various modifications andvariations of the described method and system of the invention will beapparent to those skilled in the art without departing from the scopeand spirit of the invention. Although the invention has been describedin connection with specific preferred embodiments, it should beunderstood that the invention as claimed should not be unduly limited tosuch specific embodiments. Indeed, various modifications of thedescribed modes for carrying out the invention which are obvious tothose skilled in surgical and other medical procedures, as well astransplant and grafting science, and/or related fields are intended tobe within the scope of the following claims.

What is claimed is:
 1. A device for maintaining a surgical field in anisolated environment comprising an enclosure for separating saidsurgical field from an atmosphere ambient to said device, and at leastone access port, wherein said access port enables admission into saidenclosure.
 2. The device of claim 1, wherein said at least one accessport enables admission of at least one surgical means into saidenclosure.
 3. The device of claim 2, wherein said surgical means isselected from the group consisting of surgical instruments, robotics,sensors, and human hands.
 4. The device of claim 1, wherein said devicefurther comprises means for evacuating said isolated environment.
 5. Thedevice of claim 4, wherein said evacuating produces an environment withreduced oxygen tension.
 6. The device of claim 5, wherein said reducedoxygen tension is essentially oxygen-free.
 7. The device of claim 4,wherein said device further comprises means for refilling said isolatedenvironment.
 8. The device of claim 7, wherein said refilling producesan environment with reduced oxygen tension.
 9. The device of claim 8,wherein said reduced oxygen tension is essentially oxygen-free.
 10. Thedevice of claim 7, wherein said refilling produces an environment withan increased oxygen tension.
 11. The device of claim 1, wherein saiddevice further comprises means for filling said isolated environment.12. The device of claim 11, wherein said filling produces an environmentwith reduced oxygen tension.
 13. The device of claim 11, wherein saidfilling produces an environment with an increased oxygen tension. 14.The device of claim 1, wherein said isolated environment is essentiallypathogen-free.
 15. The device of claim 1, further comprising a transportattachment.
 16. The device of claim 15, wherein said transportattachment is lockingly engaged to said device.
 17. The device of claim15, wherein said transport attachment is detachably engaged to saiddevice.
 18. The device of claim 15, wherein said transport attachmenthas a reduced oxygen tension.
 19. A device for maintaining an injuredarea in an isolated environment comprising an enclosure for separatingsaid injured area from the atmosphere ambient to said device, whereinthe oxygen tension of said isolated environment is controllable.
 20. Thedevice of claim 19, wherein said device comprises at least one accessport.
 21. The device of claim 19, wherein said device further comprisesmeans for evacuating said isolated environment.
 22. The device of claim21, wherein said evacuating comprises means for oxygen release andretention of a heavy gas within said isolated environment.
 23. Thedevice of claim 21, wherein said evacuating produces an environment withreduced oxygen tension.
 24. The device of claim 23, wherein said reducedoxygen tension is essentially oxygen-free.
 25. The device of claim 21,wherein said device further comprises means for refilling said isolatedenvironment.
 26. The device of claim 24, wherein said refilling producesan environment with reduced oxygen tension.
 27. The device of claim 25,wherein said reduced oxygen tension is essentially oxygen-free.
 28. Thedevice of claim 21, wherein said isolated environment has an increasedoxygen tension.
 29. The device of claim 19, wherein said device furthercomprises means for filling said isolated environment.
 30. The device ofclaim 29, wherein said filling produces an environment with reducedoxygen tension.
 31. The device of claim 30, wherein said reduced oxygentension is essentially oxygen-free.
 32. The device of claim 29, whereinsaid filling produces an environment with an increased oxygen tension.33. The device of claim 19, wherein said isolated environment isessentially pathogen-free.
 34. The device of claim 19, furthercomprising a transport attachment, wherein said transport attachment islockingly and detachably engaged to said device.
 35. The device of claim34, wherein said transport attachment has a reduced oxygen tension. 36.The device of claim 19, wherein said injured area is selected from thegroup consisting of surgical incisions, burns, lesions, and brokenbones.
 37. A device for maintaining material in an isolated environmentcomprising an enclosure for separating said material from an atmosphereambient to said device, wherein the oxygen tension of said isolatedenvironment is controllable.
 38. The device of claim 37, wherein saiddevice comprises at least one access port.
 39. The device of claim 37,wherein said device further comprises means for evacuating said isolatedenvironment.
 40. The device of claim 39, wherein said evacuatingcomprises means for oxygen release and retention of a heavy gas withinsaid isolated environment.
 41. The device of claim 39, wherein saidevacuating produces an environment with reduced oxygen tension.
 42. Thedevice of claim 41, wherein said reduced oxygen tension is essentiallyoxygen-free.
 43. The device of claim 41, wherein said device furthercomprises means for refilling said isolated environment.
 44. The deviceof claim 43, wherein said refilling produces an environment with reducedoxygen tension.
 45. The device of claim 44, wherein said reduced oxygentension is essentially oxygen-free.
 46. The device of claim 43, whereinsaid refilling produces an environment with an increased oxygen tension.47. The device of claim 37, wherein said device further comprises meansfor filling said isolated environment.
 48. The device of claim 47,wherein said filling produces an environment with reduced oxygentension.
 49. The device of claim 48, wherein said reduced oxygen tensionis essentially oxygen-free.
 50. The device of claim 47, wherein saidfilling produces an environment with an increased oxygen tension. 51.The device of claim 37, wherein said isolated environment is essentiallypathogen-free.
 52. The device of claim 37, wherein said material istransplant material.
 53. The device of claim 52, wherein said transplantmaterial is selected from the group consisting of organs, tissues,cells, and artificial materials.
 54. The device of claim 37, whereinsaid maintaining comprises transporting said material.